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Conciliating recent findings from molecular genetics, evolutionary biology, and clinical observations together point to new understandings regarding the mechanism, development and the persistent worldwide prevalence of major mental disorders (MMDs), which should be considered the result of an evolutionary downside trade off. Temperamental/trait variability, by facilitating choices for individual and group responses, confers robustness flexibility and resilience crucial to success of our species. Extreme temperamental variants, originating evolutionarily from the asocial aspect of human nature, also constitute the premorbid personality of the disorders. The latter create vulnerable individuals out of whom some will develop MMDs but at much higher rate to that of the general population. Significantly, similar temperamental “lopsidedness” enables many of these vulnerable individuals, if intelligent, tenacious, and curious, to be creative and contribute to our survival while some may also develop MMDs. All have a common neural-developmental origin and share characteristics in their clinical expression and pharmacological responses also expressed as mixed syndromes or alternating ones over time. Over-pruning of synaptic neurons may be considered the trigger of such occurrences or conversely, the failure to prevent them in spite of it. The symptoms of the major mental disorders are made up of antithetical substitutes as an expression of a disturbed over-all synchronizing property of brain function for all higher faculties previously unconsidered in their modeling. The concomitant presence of psychosis is a generic common occurrence.

Many oxygen mass-transfer modeling studies have been performed for various bioartificial liver (BAL) encapsulation types; yet, to our knowledge, there is no experimental study that directly and noninvasively measures viability and metabolism as a function of time and oxygen concentration. We report the effect of oxygen concentration on viability and metabolism in a fluidized-bed NMR-compatible BAL using in vivo31P and 13C NMR spectroscopy, respectively, by monitoring nucleotide triphosphate (NTP) and 13C-labeled nutrient metabolites, respectively. Fluidized-bed bioreactors eliminate the potential channeling that occurs with packed-bed bioreactors and serve as an ideal experimental model for homogeneous oxygen distribution. Hepatocytes were electrostatically encapsulated in alginate (avg. diameter, 500 μm; 3.5×107cells/mL) and perfused at 3 mL/min in a 9-cm (inner diameter) cylindrical glass NMR tube. Four oxygen treatments were tested and validated by an in-line oxygen electrode: (1) 95:5 oxygen:carbon dioxide (carbogen), (2) 75:20:5 nitrogen:oxygen:carbon dioxide, (3) 60:35:5 nitrogen:oxygen:carbon dioxide, and (4) 45:50:5 nitrogen:oxygen:carbon dioxide. With 20% oxygen, β-NTP steadily decreased until it was no longer detected at 11 h. The 35%, 50%, and 95% oxygen treatments resulted in steady β-NTP levels throughout the 28-h experimental period. For the 50% and 95% oxygen treatment, a 13C NMR time course (∼5 h) revealed 2-13C-glycine and 2-13C-glucose to be incorporated into [2-13C-glycyl]glutathione (GSH) and 2-13C-lactate, respectively, with 95% having a lower rate of lactate formation. 31P and 13C NMR spectroscopy is a noninvasive method for determining viability and metabolic rates. Modifying tissue-engineered devices to be NMR compatible is a relatively easy and inexpensive process depending on the bioreactor shape.

Structural determinants underlying signaling specificity in the tumor necrosis factor receptor superfamily (TNFRSF) are poorly characterized, and it is unclear whether different signaling outputs can be genetically dissociated. The p75 neurotrophin receptor (p75NTR), also known as TNFRSF16, is a key regulator of trophic and injury responses in the nervous system. Here, we describe a genetic approach for dissecting p75NTRsignaling and deciphering its underlying logic. Structural determinants important for regulation of cell death, NF-κB, and RhoA pathways were identified in the p75NTRdeath domain (DD). Proapoptotic and prosurvival pathways mapped onto nonoverlapping epitopes, demonstrating that different signaling outputs can be genetically separated in p75NTR. Dissociation of c-Jun kinase (JNK) and caspase-3 activities indicated that JNK is necessary but not sufficient for p75NTR-mediated cell death. RIP2 recruitment and RhoGDI release were mechanistically linked, indicating that competition for DD binding underlies crosstalk between NF-κB and RhoA pathways in p75NTRsignaling. These results provide insights into the logic of p75NTRsignaling and pave the way for a genetic dissection of p75NTRfunction and physiology.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine that is involved in many normal as well as pathological conditions. HGF/NK1, a splice variant of HGF/SF, has been reported to have either antagonistic or agonistic effects with regard to c-Met signaling depending on the cell type. In these experiments, we have determined that HGF/NK1 is a potent mitogen for rat hepatocytes in culture. Furthermore, we have found that coagulation factor Xa (fXa) is capable of cleaving HGF/NK1 and single chain HGF/SF (scHGF/SF). The products resulting from cleavage of HGF/NK1 or scHGF/SF by fXa appear as single bands under non-reducing conditions. The reaction products from the digestion of HGF/NK1 by fXa were separated under reducing conditions, and the cleavage site, as determined by N-terminal sequencing, was located C-terminal to arginine 134. Previous work established that the heparin-binding domain for HGF/SF is located in the N domain of HGF/SF. Additionally, the dimerization of the HGF/SF receptor (c-Met) by the ligand HGF/NK1 is facilitated by heparin and related sulfonated sugars on the cell surface, whereas heparin is not required for HGF/SF-mediated dimerization. Cleavage of single chain HGF/SF or HGF/NK1 by factor Xa does not alter the affinity of the respective molecules for heparin, but it did variably affect the associated mitogenic activity of these factors. The associated mitogenic activity of HGF/NK1 was reduced by more than 90%, whereas the mitogenic activity of scHGF/SF was unaffected. This suggests mandatory maintenance of a steric interaction of the N domain and the first kringle domain for HGF/NK1 to act as an agonist for rat hepatocyte growth but is not required by full-length HGF/SF.

Serum from control or partially hepatectomized rats contains only two substances associated with stimulation of DNA synthesis in primary cultures of hepatocytes in serum free conditions. Hepatopoietin A is a large (105,000 kDa in monomeric form) heparin binding growth factor that is a heterodimer of two polypeptide chains (70,000 and 35,000 kDa). Another heparin binding growth factor, acidic FGF, also stimulates hepatocyte DNA synthesis but at a level comparable to half that of HPTA. These findings, along with recent observations of stimulation of liver growth and hepatoma formation in mice transgenic for the tat gene of the AIDS virus and overproducers of the heparin binding factor hst/KS3, raise the issue of the overall importance of different heparin binding growth factors in the control of hepatic growth regulation. Hepatopoietin B is a glycolipid that also acts as a complete hepatocytic mitogen. The role of the above substances as well as the role of norepinephrine, acting as a mitogenic trigger for stimulation of the rapid early phenomena associated with liver regeneration, is discussed.

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Single crystals of ScB15are prepared from the elements in molten Ga (1600 °C, 40 h) and single crystals of Sc2Cu0.77B45are obtained from the elements in a Cu/Sc melt (1800 °C, 40 h).

Dark red single crystals of MgB7are obtained from a Cu/Mg/B melt (3:1:0.75; BN crucible in a sealed Ta tube, 1600 °C, 40 h).

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Schlufolgerung: Um einen Trophoblasttumor in der Frhschwangerschaft nicht zu verkennen und um eine inadquate Therapie zu vermeiden, sollte jede Interruptio verbunden sein mit einer properativen und evtl. auch postoperativenSonographie und vor allem mit einer histologischen Untersuchung des Schwangerschaftsgewebes.